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ARIAD Announces Recommendation for Iclusig by the Pharmacovigilance Risk Assessment Committee of the European Medicines Agency

On October 10, 2014 ARIAD Pharmaceuticals reported that the Pharmacovigilance Risk Assessment Committee (PRAC) of the European Medicines Agency (EMA) has concluded its review of Iclusig (ponatinib) under the Article 20 referral procedure and has recommended that Iclusig continue to be used in Europe in accordance with its already approved indications (Press release Ariad, OCT 10, 2014, View Source;p=RssLanding&cat=news&id=1976197 [SID:1234500818]).

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"We are grateful for the rigorous and in-depth review provided by the PRAC and the Scientific Advisory Group for Oncology," stated Harvey J. Berger, M.D., chairman and chief executive officer of ARIAD. "The PRAC recommendation provides insightful guidance to healthcare professionals and patients regarding the use of Iclusig in patients with Ph+ leukemias and importantly, leaves the original Iclusig indication statement unchanged. We look forward to consideration and adoption of these recommendations by the CHMP later this month and authorization by the European Commission by the end of the year."

The authorized indications of Iclusig in Europe, as approved in July 2013, are as follows:

The treatment of adult patients with chronic phase, accelerated phase or blast phase chronic myeloid leukaemia (CML) who are resistant to dasatinib or nilotinib; who are intolerant to dasatinib or nilotinib and for whom subsequent treatment with imatinib is not clinically appropriate; or who have the T315I mutation, or
The treatment of adult patients with Philadelphia-chromosome positive acute lymphoblastic leukaemia (Ph+ ALL) who are resistant to dasatinib; who are intolerant to dasatinib and for whom subsequent treatment with imatinib is not clinically appropriate; or who have the T315I mutation.

Other recommendations made by the PRAC related to the Iclusig Summary of Medicinal Product Characteristics (SmPC) include, (1) patient monitoring for response according to standard clinical guidelines, (2) consideration of Iclusig dose-reduction following achievement of major cytogenetic response with subsequent monitoring of response and, (3) consideration of Iclusig discontinuation if a complete haematologic response has not been achieved by three months. Further information is provided indicating that the risk of vascular occlusive events is likely dose-related. An update of the Warning and Precautions and Undesirable Effects sections is also provided for inclusion in the Iclusig SmPC.

"The recommendation from the PRAC confirms a positive benefit-risk assessment for Iclusig after thorough consideration of updated safety information," said Stephen G. O’Brien, M.D., Ph.D., Professor of Haematology at the Northern Institute for Cancer Research at Newcastle University, United Kingdom. "This is a good outcome for patients and healthcare professionals in Europe as it continues to offer a treatment option to CML patients who have become resistant to, or intolerant of, certain other TKIs."

The PRAC is the committee at the EMA that is responsible for assessing and monitoring safety issues for human medicines. The PRAC’s recommendations are considered by the CHMP when it adopts opinions for centrally authorized medicines and referral procedures.

Vernalis licenses V2006 to RedoxTherapies Inc for use in immuno-oncology

On October 9, 2014 Vernalis plc reported that it has licensed worldwide rights in vipadenant (V2006), a small molecule A2A receptor antagonist, to RedoxTherapies Inc (Redox) (Press release, Vernalis, OCT 9, 2014, View Source [SID:1234513891]). Vipadenant has the potential to disrupt an immunosuppressive mechanism of tumor protection, generating improved efficacy for immunotherapies of certain cancers when used in combination.

Redox is a private, Boston-based start-up company that is the exclusive licensee of National Institute of Health (USA) intellectual property in the field of using extracellular adenosine receptor inhibitors in combination with immuno-oncology therapies.

The detailed financial terms of the Licence Agreement with Redox are not disclosed, but Vernalis can earn milestones and royalties on successful clinical, regulatory and commercial advancement.

Commenting on the new relationship, Ian Garland, CEO of Vernalis said "We look forward to having Redox as a partner and to the progress of vipadenant into clinical studies in this exciting new setting for the potential benefit of cancer patients worldwide".

(Press release, Intensity Therapeutics, OCT 9, 2014, View Source [SID:1234503398])

FDA Approves VELCADE® (bortezomib) for Injection for Previously Untreated Patients with Mantle Cell Lymphoma

On October 9, 2014 Takeda reported that the U.S. Food and Drug Administration (FDA) has approved VELCADE (bortezomib) for injection for use in previously untreated patients with mantle cell lymphoma (MCL) (Press release Takeda, OCT 9, 2014, View Source [SID:1234500832]). VELCADE is the first treatment in the United States to be approved for use in previously untreated patients with MCL. This approval extends the utility of VELCADE beyond relapsed or refractory mantle cell lymphoma, for which it has been approved since 2006.

"Mantle cell lymphoma is a subtype of non-Hodgkin lymphoma that is usually a clinically aggressive malignancy, and it is a challenging disease to treat in part due to a relatively high risk of relapse," said Andrew Evens, DO, MSc, Director, Tufts Cancer Center; Chief, Division of Hematology/Oncology; Director, Lymphoma Program. "There are several new targeted drugs approved by the FDA for patients with relapsed or refractory disease, but up to this point, there had been none approved for the treatment of patients with previously untreated disease. VELCADE, when used in the VcR-CAP regimen, VELCADE, rituximab, cyclophosphamide, doxorubicin and prednisone, has demonstrated improved outcomes for patients, making it an important advance for the treatment of newly-diagnosed patients with mantle cell lymphoma."

This approval is based on the results of an international, randomized, head-to-head Phase 3 study that showed that previously untreated patients receiving a VELCADE-containing combination (VcR-CAP) experienced a 59 percent relative improvement in the study’s primary endpoint of progression-free survival (PFS) compared to those who were administered the standard R-CHOP (rituximab, cyclophosphamide, doxorubicin, vincristine and prednisone) regimen (median 25 vs. 14 months; Hazard Ratio [HR] 0.63; P < 0.001) at a median follow up of 40 months. An Independent Review Committee (IRC) assessed the primary efficacy endpoint of PFS. The complete response (CR) rate for patients receiving VcR-CAP vs. R-CHOP was 44 percent vs. 34 percent.

"We are delighted VELCADE has received approval in previously untreated mantle cell lymphoma. The VELCADE-combination delivered an 11-month median advantage in progression-free survival as compared to a current standard of care," said Dixie-Lee Esseltine, MD, FRCPC, Vice President, Oncology Clinical Research, Takeda Pharmaceuticals International Co. "Since 2006, VELCADE has proven to be an important therapy for the treatment of relapsed or refractory mantle cell lymphoma, and it can now be used as an initial treatment for all patients with mantle cell lymphoma."

The open-label, multicenter, prospective study evaluated the efficacy and safety of VcR-CAP vs. R-CHOP in 487 patients with previously untreated MCL who were ineligible or not considered for a bone marrow transplant. VELCADE (1.3 mg/m2) is administered intravenously in combination with intravenous rituximab, cyclophosphamide, doxorubicin and oral prednisone (VcR-CAP) for six 3-week treatment cycles. VELCADE is administered first followed by rituximab. VELCADE is administered twice weekly for two weeks (days 1, 4, 8 and 11) followed by a 10‑day rest period on days 12‑21. For patients with a response first documented at cycle 6, two additional VcR-CAP cycles are recommended. At least 72 hours should elapse between consecutive doses of VELCADE.

The most common adverse reactions occurring in ≥20 percent of patients receiving the VcR-CAP regimen were neutropenia, leukopenia, anemia, thrombocytopenia, lymphopenia, peripheral neuropathy, pyrexia, nausea and diarrhea. Infections were reported for 31 percent of patients in the VcR-CAP arm and 23 percent of the patients in the R-CHOP arm including pneumonia (8 percent versus 5 percent). Adverse reactions leading to discontinuation occurred in 8 percent of patients in the VcR-CAP arm and 6 percent of patients in the R-CHOP arm. In the VcR-CAP group, the most commonly reported adverse reaction leading to discontinuation was peripheral sensory neuropathy (1 percent; 3 patients).

Cyclacel Announces Data Safety Monitoring Board Recommendation to Continue the Seamless Phase 3 Trial of Sapacitabine in AML

On October 9, 2014 Cyclacel Pharmaceuticals reported that the independent Data and Safety Monitoring Board (DSMB) for the Company’s Phase 3 SEAMLESS study in acute myeloid leukemia (AML) has completed its fourth planned safety review and recommended that the study should continue as planned without any modifications (Press release Cyclacel, OCT 9, 2014, View Source [SID:1234500809]). The DSMB reviewed available data from 317 randomized patients with at least 60 days of follow-up and noted that no safety or efficacy concerns were identified.

"This is the fourth consecutive review for which the DSMB recommended that the SEAMLESS study should continue as planned," said Judy H. Chiao, M.D., Vice President, Clinical Development and Regulatory Affairs of Cyclacel. "We are encouraged by the DSMB’s recommendation based on their review of available data from US and European sites participating in SEAMLESS. We now have over 100 US and European sites open and expect completion of enrollment to occur in the next few months. In addition to SEAMLESS, we are conducting feasibility assessment of our Phase 2b randomized study of sapacitabine in older patients with myelodysplastic syndromes (MDS) after treatment failure of hypomethylating agents."

SEAMLESS is a Phase 3, randomized, registration-directed study of oral sapacitabine capsules in elderly (70 years or older) patients with AML who are unfit for or have refused intensive chemotherapy. The primary endpoint is overall survival. SEAMLESS is being conducted under a Special Protocol Assessment (SPA) agreement with the U.S. Food and Drug Administration (FDA). The DSMB will perform an interim analysis for futility once half of the required events have been observed.